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Late blight, caused by the oomycete Phytophthora infestans, poses a significant challenge to organic tomato and potato production systems across the globe. To enhance education and outreach programming pertaining to tomato organic late blight management in Wisconsin, we sought to identify grower strategies and needs through an online survey conducted during spring 2018. Our findings demonstrated that organic growers emphasized crop diversity, crop rotation and soil health in their late blight management decisions. Grower concerns about biopesticides were identified and suggest that the use of input-based products within integrated management programs could be enhanced by further research on effectiveness and modes of actions. Additionally, stronger emphasis on oomycete pathogen biology and the significance of late blight as a community disease were identified as important areas of emphasis in the development of organic disease management education programming and resources that promote more effective cultural and chemical disease management strategies that adhere to the regulation and principles underlying the USDA National Organic Program. The integration of a live polling questionnaire conducted in winter 2019 allowed us to corroborate findings from the online survey and underscored the importance of two-way learning to enhance outreach efforts between Extension and organic growers in Wisconsin and the surrounding upper Midwestern states.
Influenza virus infections can lead to a number of secondary complications, including sepsis. We applied linear regression models to mortality and hospital admission data coded for septicaemia from 1998 to 2019 in Hong Kong, and estimated that septicaemia was associated with an annual average excess mortality rate of 0.23 (95% CI 0.04–0.40) per 100 000 persons per year and an excess septicaemia hospitalisation rate of 1.73 (95% CI 0.94–2.50) per 100 000 persons per year. The highest excess morbidity and mortality was found in older adults and young children, and during influenza A(H3N2) epidemics.
Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.
To determine the impact of clinical decision support on guideline-concordant Clostridioides difficile infection (CDI) treatment.
Design:
Quasi-experimental study in >50 ambulatory clinics.
Setting:
Primary, specialty, and urgent-care clinics.
Patients:
Adult patients were eligible for inclusion if they were diagnosed with and treated for a first episode of symptomatic CDI at an ambulatory clinic between November 1, 2019, and November 30, 2020.
Interventions:
An outpatient best practice advisory (BPA) was implemented to notify prescribers that “vancomycin or fidaxomicin are preferred over metronidazole for C.difficile infection” when metronidazole was prescribed to a patient with CDI.
Results:
In total, 189 patients were included in the study: 92 before the BPA and 97 after the BPA. Their median age was 59 years; 31% were male; 75% were white; 30% had CDI-related comorbidities; 35% had healthcare exposure; 65% had antibiotic exposure; 44% had gastric acid suppression therapy within 90 days of CDI diagnosis. The BPA was accepted 23 of 26 times and was used to optimize the therapy of 16 patients in 6 months. Guideline-concordant therapy increased after implementation of the BPA (72% vs 91%; P = .001). Vancomycin prescribing increased and metronidazole prescribing decreased after the BPA. There was no difference in clinical response or unplanned encounter within 14 days after treatment initiation. Fewer patients after the BPA had CDI recurrence within 14–56 days of the initial episode (27% vs 7%; P < .001).
Conclusions:
Clinical decision support increased prescribing of guideline-concordant CDI therapy in the outpatient setting. A targeted BPA is an effective stewardship intervention and may be especially useful in settings with limited antimicrobial stewardship resources.
The most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.
Methods
Face-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents.
Results
3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2–4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness.
Conclusion
ADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.
The GaLactic and Extragalactic All-sky Murchison Widefield Array (GLEAM) is a radio continuum survey at 76–227 MHz of the entire southern sky (Declination
$<\!{+}30^{\circ}$
) with an angular resolution of
${\approx}2$
arcmin. In this paper, we combine GLEAM data with optical spectroscopy from the 6dF Galaxy Survey to construct a sample of 1 590 local (median
$z \approx 0.064$
) radio sources with
$S_{200\,\mathrm{MHz}} > 55$
mJy across an area of
${\approx}16\,700\,\mathrm{deg}^{2}$
. From the optical spectra, we identify the dominant physical process responsible for the radio emission from each galaxy: 73% are fuelled by an active galactic nucleus (AGN) and 27% by star formation. We present the local radio luminosity function for AGN and star-forming (SF) galaxies at 200 MHz and characterise the typical radio spectra of these two populations between 76 MHz and
${\sim}1$
GHz. For the AGN, the median spectral index between 200 MHz and
${\sim}1$
GHz,
$\alpha_{\mathrm{high}}$
, is
$-0.600 \pm 0.010$
(where
$S \propto \nu^{\alpha}$
) and the median spectral index within the GLEAM band,
$\alpha_{\mathrm{low}}$
, is
$-0.704 \pm 0.011$
. For the SF galaxies, the median value of
$\alpha_{\mathrm{high}}$
is
$-0.650 \pm 0.010$
and the median value of
$\alpha_{\mathrm{low}}$
is
$-0.596 \pm 0.015$
. Among the AGN population, flat-spectrum sources are more common at lower radio luminosity, suggesting the existence of a significant population of weak radio AGN that remain core-dominated even at low frequencies. However, around 4% of local radio AGN have ultra-steep radio spectra at low frequencies (
$\alpha_{\mathrm{low}} < -1.2$
). These ultra-steep-spectrum sources span a wide range in radio luminosity, and further work is needed to clarify their nature.
We present a high-resolution seawater radiocarbon (Δ14C) record from a Porites coral collected from Masthead Island in the southern Great Barrier Reef (GBR) covering the years 1945–2017. The Δ14C values from 1945–1953 (pre-bomb era) averaged –49‰. As a result of bomb-produced 14C in the atmosphere, Δ14C values started to rise rapidly from 1959, levelled off at ∼131‰ in the late 1970s and gradually decreased to ∼40.3‰ by 2017 due to the decrease in the air-sea 14C gradient and the overturning of the 14C ocean reservoir (i.e., surface ocean to subsurface ocean; atmosphere to surface ocean). The Masthead Island record is in agreement with previous 14C coral records from the southern GBR. A comparison between surface ocean and atmospheric Δ14C suggests that, since 2010, the main reservoir of bomb-derived 14C has shifted from the atmosphere to the surface ocean, potentially resulting in reversed 14C flux in regions where the CO2 gradient is favorable. The high-resolution Masthead coral Δ14C sheds light on long-term variability in air-sea exchange and GBR regional ocean dynamics associated with climate change and in conjunction with the previous records provides a robust seawater 14C reference series to date other carbonate samples.
To investigate the influences of dietary riboflavin (RF) addition on nutrient digestion and rumen fermentation, eight rumen cannulated Holstein bulls were randomly allocated into four treatments in a repeated 4 × 4 Latin square design. Daily addition level of RF for each bull in control, low RF, medium RF and high RF was 0, 300, 600 and 900 mg, respectively. Increasing the addition level of RF, DM intake was not affected, average daily gain tended to be increased linearly and feed conversion ratio decreased linearly. Total tract digestibilities of DM, organic matter, crude protein (CP) and neutral-detergent fibre (NDF) increased linearly. Rumen pH decreased quadratically, and total volatile fatty acids (VFA) increased quadratically. Acetate molar percentage and acetate:propionate ratio increased linearly, but propionate molar percentage and ammonia-N content decreased linearly. Rumen effective degradability of DM increased linearly, NDF increased quadratically but CP was unaltered. Activity of cellulase and populations of total bacteria, protozoa, fungi, dominant cellulolytic bacteria, Prevotella ruminicola and Ruminobacter amylophilus increased linearly. Linear increase was observed for urinary total purine derivatives excretion. The data suggested that dietary RF addition was essential for rumen microbial growth, and no further increase in performance and rumen total VFA concentration was observed when increasing RF level from 600 to 900 mg/d in dairy bulls.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
To evaluate the impacts of guanidinoacetic acid (GAA) and coated folic acid (CFA) on growth performance, nutrient digestion and hepatic gene expression, fifty-two Angus bulls were assigned to four groups in a 2 × 2 factor experimental design. The CFA of 0 or 6 mg/kg dietary DM folic acid was supplemented in diets with GAA of 0 (GAA−) or 0·6 g/kg DM (GAA+), respectively. Average daily gain (ADG), feed efficiency and hepatic creatine concentration increased with GAA or CFA addition, and the increased magnitude of these parameters was greater for addition of CFA in GAA− diets than in GAA+ diets. Blood creatine concentration increased with GAA or CFA addition, and greater increase was observed when CFA was supplemented in GAA+ diets than in GAA− diets. DM intake was unchanged, but rumen total SCFA concentration and digestibilities of DM, crude protein, neutral-detergent fibre and acid-detergent fibre increased with the addition of GAA or CFA. Acetate:propionate ratio was unaffected by GAA, but increased for CFA addition. Increase in blood concentrations of albumin, total protein and insulin-like growth factor-1 (IGF-1) was observed for GAA or CFA addition. Blood folate concentration was decreased by GAA, but increased with CFA addition. Hepatic expressions of IGF-1, phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin and ribosomal protein S6 kinase increased with GAA or CFA addition. Results indicated that the combined supplementation of GAA and CFA could not cause ADG increase more when compared with GAA or CFA addition alone.
Data on the prevalence of extrapulmonary tuberculosis (EPTB) patients are limited in many African countries including Malawi. We conducted a retrospective review of all histology reports for cancer suspected patients at Mzuzu Central Hospital (MZCH) between 2013 and 2018 to determine the proportion of EPTB cases among cancer suspected patients and characterised them epidemiologically. All reports with inconclusive findings were excluded. In total, 2214 reports were included in the review, 47 of which reported EPTB, representing 2.1% (95% CI 1.6−2.8). The incidence of EPTB was significantly associated with sex, age and HIV status. Men were more than twice (OR 2.1; 95% CI 1.2–3.9) as likely to have EPTB as women while those with HIV were more than six times (OR 6.4; 95% CI 1.7–24.8) as likely to have EPTB compared to those who were HIV-negative. EPTB demonstrated an inverse relationship with age. The highest proportion of EPTB was found from neck lymph nodes (10.3% (5.4–17.2)). A reasonable number of EPTB cases are diagnosed late or missed in Malawi's hospitals. There is a need for concerted efforts to increase EPTB awareness and likely come up with a policy to consider EPTB as a differential diagnosis in cancer suspected patients.
The Murchison Widefield Array (MWA) has observed the entire southern sky (Declination,
$\delta< 30^{\circ}$
) at low radio frequencies, over the range 72–231MHz. These observations constitute the GaLactic and Extragalactic All-sky MWA (GLEAM) Survey, and we use the extragalactic catalogue (EGC) (Galactic latitude,
$|b| >10^{\circ}$
) to define the GLEAM 4-Jy (G4Jy) Sample. This is a complete sample of the ‘brightest’ radio sources (
$S_{\textrm{151\,MHz}}>4\,\text{Jy}$
), the majority of which are active galactic nuclei with powerful radio jets. Crucially, low-frequency observations allow the selection of such sources in an orientation-independent way (i.e. minimising the bias caused by Doppler boosting, inherent in high-frequency surveys). We then use higher-resolution radio images, and information at other wavelengths, to morphologically classify the brightest components in GLEAM. We also conduct cross-checks against the literature and perform internal matching, in order to improve sample completeness (which is estimated to be
$>95.5$
%). This results in a catalogue of 1863 sources, making the G4Jy Sample over 10 times larger than that of the revised Third Cambridge Catalogue of Radio Sources (3CRR;
$S_{\textrm{178\,MHz}}>10.9\,\text{Jy}$
). Of these G4Jy sources, 78 are resolved by the MWA (Phase-I) synthesised beam (
$\sim2$
arcmin at 200MHz), and we label 67% of the sample as ‘single’, 26% as ‘double’, 4% as ‘triple’, and 3% as having ‘complex’ morphology at
$\sim1\,\text{GHz}$
(45 arcsec resolution). We characterise the spectral behaviour of these objects in the radio and find that the median spectral index is
$\alpha=-0.740 \pm 0.012$
between 151 and 843MHz, and
$\alpha=-0.786 \pm 0.006$
between 151MHz and 1400MHz (assuming a power-law description,
$S_{\nu} \propto \nu^{\alpha}$
), compared to
$\alpha=-0.829 \pm 0.006$
within the GLEAM band. Alongside this, our value-added catalogue provides mid-infrared source associations (subject to 6” resolution at 3.4
$\mu$
m) for the radio emission, as identified through visual inspection and thorough checks against the literature. As such, the G4Jy Sample can be used as a reliable training set for cross-identification via machine-learning algorithms. We also estimate the angular size of the sources, based on their associated components at
$\sim1\,\text{GHz}$
, and perform a flux density comparison for 67 G4Jy sources that overlap with 3CRR. Analysis of multi-wavelength data, and spectral curvature between 72MHz and 20GHz, will be presented in subsequent papers, and details for accessing all G4Jy overlays are provided at https://github.com/svw26/G4Jy.
The entire southern sky (Declination,
$\delta< 30^{\circ}$
) has been observed using the Murchison Widefield Array (MWA), which provides radio imaging of
$\sim$
2 arcmin resolution at low frequencies (72–231 MHz). This is the GaLactic and Extragalactic All-sky MWA (GLEAM) Survey, and we have previously used a combination of visual inspection, cross-checks against the literature, and internal matching to identify the ‘brightest’ radio-sources (
$S_{\mathrm{151\,MHz}}>4$
Jy) in the extragalactic catalogue (Galactic latitude,
$|b| >10^{\circ}$
). We refer to these 1 863 sources as the GLEAM 4-Jy (G4Jy) Sample, and use radio images (of
${\leq}45$
arcsec resolution), and multi-wavelength information, to assess their morphology and identify the galaxy that is hosting the radio emission (where appropriate). Details of how to access all of the overlays used for this work are available at https://github.com/svw26/G4Jy. Alongside this we conduct further checks against the literature, which we document here for individual sources. Whilst the vast majority of the G4Jy Sample are active galactic nuclei with powerful radio-jets, we highlight that it also contains a nebula, two nearby, star-forming galaxies, a cluster relic, and a cluster halo. There are also three extended sources for which we are unable to infer the mechanism that gives rise to the low-frequency emission. In the G4Jy catalogue we provide mid-infrared identifications for 86% of the sources, and flag the remainder as: having an uncertain identification (129 sources), having a faint/uncharacterised mid-infrared host (126 sources), or it being inappropriate to specify a host (2 sources). For the subset of 129 sources, there is ambiguity concerning candidate host-galaxies, and this includes four sources (B0424–728, B0703–451, 3C 198, and 3C 403.1) where we question the existing identification.
Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.
Methods:
Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.
Results:
The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.
Conclusions:
Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.
Symptoms of attention-deficit/hyperactivity disorder (ADHD) appear in childhood, but often persist into adulthood. The prodrug lisdexamfetamine dimesylate (LDX) is an effective once-daily treatment for the symptoms of ADHD in children, adolescent and adults.
Objectives
To evaluate post hoc the impact of ADHD medication history on the efficacy of LDX in adults.
Methods
In this phase 4, double-blind, dose-optimized study, patients aged 18–55 with ADHD and impaired executive function were randomized (1:1) to LDX or placebo for 10 weeks. Patients well controlled on current ADHD medication with acceptable tolerability were ineligible. Self-reported, lifetime ADHD medication histories were recorded at screening. Investigator-rated ADHD Rating Scale IV with adult prompts (ADHD-RS-IV-Adult) was a secondary efficacy measure. Primary efficacy and safety outcomes have been published (J Clin Psychiatry 2013;74:694–702).
Results
Baseline characteristics were similar across treatment arms and previous ADHD medication subgroups. Differences between LDX and placebo in mean change from baseline to endpoint in ADHD-RS-IV-Adult total score were observed in the overall study population (n=154; –11.1 [95% confidence interval: –14.96, –7.32]; effect size, 0.9), treatment-naïve patients (n=80; –11.4 [–16.81, –5.96]; 0.9) and patients previously treated with: any ADHD medication (n=74; –10.9 [–16.50, –5.30]; 0.9), methylphenidate (n=40; –9.9 [–17.44, –2.45]; 0.9), amfetamine (n=38; –13.8 [–20.86, –6.75]; 1.3) and atomoxetine (n=21; –8.4 [–21.97, +5.26]; 0.6).
Conclusion
In these post hocanalyses, the response to LDX was similar in the overall study population and subgroups of patients categorized by ADHD medication history.
Observational studies have linked elevated homocysteine to vascular conditions. Folate intake has been associated with lower homocysteine concentration, although randomised controlled trials of folic acid supplementation to decrease the incidence of vascular conditions have been inconclusive. We investigated determinants of maternal homocysteine during pregnancy, particularly in a folic acid-fortified population.
Design:
Data were from the Ottawa and Kingston Birth Cohort of 8085 participants. We used multivariable regression analyses to identify factors associated with maternal homocysteine, adjusted for gestational age at bloodwork. Continuous factors were modelled using restricted cubic splines. A subgroup analysis examined the modifying effect of MTHFR 677C>T genotype on folate, in determining homocysteine concentration.
Setting:
Participants were recruited in Ottawa and Kingston, Canada, from 2002 to 2009.
Participants:
Women were recruited when presenting for prenatal care in the early second trimester.
Results:
In 7587 participants, factors significantly associated with higher homocysteine concentration were nulliparous, smoking and chronic hypertension, while factors significantly associated with lower homocysteine concentration were non-Caucasian race, history of a placenta-mediated complication and folic acid supplementation. Maternal age and BMI demonstrated U-shaped associations. Folic acid supplementation of >1 mg/d during pregnancy did not substantially increase folate concentration. In the subgroup analysis, MTHFR 677C>T modified the effect of folate status on homocysteine concentration.
Conclusions:
We identified determinants of maternal homocysteine relevant to the lowering of homocysteine in the post-folic acid fortification era, characterised by folate-replete populations. A focus on periconceptional folic acid supplementation and improving health status may form an effective approach to lower homocysteine.
While previous studies have described career outcomes of physician-scientist trainees after graduation, trainee perceptions of research-intensive career pathways remain unclear. This study sought to identify the perceived interests, factors, and challenges associated with academic and research careers among predoctoral MD trainees, MD trainees with research-intense (>50%) career intentions (MD-RI), and MD-PhD trainees.
Methods:
A 70-question survey was administered to 16,418 trainees at 32 academic medical centers from September 2012 to December 2014. MD vs. MD-RI (>50% research intentions) vs. MD-PhD trainee responses were compared by chi-square tests. Multivariate logistic regression analyses were performed to identify variables associated with academic and research career intentions.
Results:
There were 4433 respondents (27% response rate), including 2625 MD (64%), 653 MD-RI (15%), and 856 MD-PhD (21%) trainees. MD-PhDs were most interested in pursuing academia (85.8%), followed by MD-RIs (57.3%) and MDs (31.2%). Translational research was the primary career intention for MD-PhD trainees (42.9%). Clinical duties were the primary career intention for MD-RIs (51.9%) and MDs (84.2%). While 39.8% of MD-PhD respondents identified opportunities for research as the most important career selection factor, only 12.9% of MD-RI and 0.5% of MD respondents shared this perspective. Interest in basic research, translational research, clinical research, education, and the ability to identify a mentor were each independently associated with academic career intentions by multivariate regression.
Conclusions:
Predoctoral MD, MD-RI, and MD-PhD trainees are unique cohorts with different perceptions and interests toward academic and research careers. Understanding these differences may help to guide efforts to mentor the next generation of physician-scientists.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
$60+$
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.